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. 1992 Jun 25;20(12):3183–3189. doi: 10.1093/nar/20.12.3183

Characterization of the testes-specific pim-1 transcript in rat.

D Wingett 1, R Reeves 1, N S Magnuson 1
PMCID: PMC312457  PMID: 1620615

Abstract

The pim-1 proto-oncogene encodes a serine/threonine protein kinase and is expressed in cells of hematolymphoid origin and in the germ cell lineages. In somatic cells, the pim-1 gene is expressed as a 2.8 kb transcript while a shorter sized transcript (2.3 kb) is expressed in rat testes. We have determined that the shorter testes-specific pim-1 transcript arises through the use of an alternate polyadenylation signal present in the 3' untranslated region of the gene. This alternate polyadenylation event results in the removal of an A/U-rich regulatory element located in the 3' untranslated region of the pim-1 gene. This A/U-rich motif has been shown by a number of laboratories to destabilize the transcripts of genes that contain this sequence. Consistent with these findings, we have demonstrated that the shortened testes-specific pim-1 transcript is more stable than the longer A/U-rich containing somatic transcript. We suggest that the functional significance of different sized pim-1 transcripts may be directly related to their different stabilities and that the greater stability of the testes-specific transcript may be essential for the translational delay observed in post-meiotic male germ cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amson R., Sigaux F., Przedborski S., Flandrin G., Givol D., Telerman A. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8857–8861. doi: 10.1073/pnas.86.22.8857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bellvé A. R., Cavicchia J. C., Millette C. F., O'Brien D. A., Bhatnagar Y. M., Dym M. Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J Cell Biol. 1977 Jul;74(1):68–85. doi: 10.1083/jcb.74.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berget S. M. Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature. 1984 May 10;309(5964):179–182. doi: 10.1038/309179a0. [DOI] [PubMed] [Google Scholar]
  4. Bohjanen P. R., Petryniak B., June C. H., Thompson C. B., Lindsten T. AU RNA-binding factors differ in their binding specificities and affinities. J Biol Chem. 1992 Mar 25;267(9):6302–6309. [PubMed] [Google Scholar]
  5. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  6. Cuypers H. T., Selten G., Quint W., Zijlstra M., Maandag E. R., Boelens W., van Wezenbeek P., Melief C., Berns A. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell. 1984 May;37(1):141–150. doi: 10.1016/0092-8674(84)90309-x. [DOI] [PubMed] [Google Scholar]
  7. Dautry F., Weil D., Yu J., Dautry-Varsat A. Regulation of pim and myb mRNA accumulation by interleukin 2 and interleukin 3 in murine hematopoietic cell lines. J Biol Chem. 1988 Nov 25;263(33):17615–17620. [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Domen J., Von Lindern M., Hermans A., Breuer M., Grosveld G., Berns A. Comparison of the human and mouse PIM-1 cDNAs: nucleotide sequence and immunological identification of the in vitro synthesized PIM-1 protein. Oncogene Res. 1987 Jun;1(1):103–112. [PubMed] [Google Scholar]
  10. Dorfman D. M., Zon L. I., Orkin S. H. Rapid amplification of lambda gt11 bacteriophage library inserts from plaques using the polymerase chain reaction (PCR). Biotechniques. 1989 Jun;7(6):568–570. [PubMed] [Google Scholar]
  11. Dorrington J. H., Roller N. F., Fritz I. B. Effects of follicle-stimulating hormone on cultures of Sertoli cell preparations. Mol Cell Endocrinol. 1975 Jul;3(1):57–70. doi: 10.1016/0303-7207(75)90031-3. [DOI] [PubMed] [Google Scholar]
  12. Fischman K., Edman J. C., Shackleford G. M., Turner J. A., Rutter W. J., Nir U. A murine fer testis-specific transcript (ferT) encodes a truncated Fer protein. Mol Cell Biol. 1990 Jan;10(1):146–153. doi: 10.1128/mcb.10.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Geremia R., Boitani C., Conti M., Monesi V. RNA synthesis in spermatocytes and spermatids and preservation of meiotic RNA during spermiogenesis in the mouse. Cell Differ. 1977 Mar;5(5-6):343–355. doi: 10.1016/0045-6039(77)90072-0. [DOI] [PubMed] [Google Scholar]
  14. Hanukoglu I., Tanese N., Fuchs E. Complementary DNA sequence of a human cytoplasmic actin. Interspecies divergence of 3' non-coding regions. J Mol Biol. 1983 Feb 5;163(4):673–678. doi: 10.1016/0022-2836(83)90117-1. [DOI] [PubMed] [Google Scholar]
  15. Heidaran M. A., Kistler W. S. Transcriptional and translational control of the message for transition protein 1, a major chromosomal protein of mammalian spermatids. J Biol Chem. 1987 Sep 25;262(27):13309–13315. [PubMed] [Google Scholar]
  16. Hoover D., Friedmann M., Reeves R., Magnuson N. S. Recombinant human pim-1 protein exhibits serine/threonine kinase activity. J Biol Chem. 1991 Jul 25;266(21):14018–14023. [PubMed] [Google Scholar]
  17. Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
  18. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249–270. doi: 10.1016/0092-8674(91)90637-e. [DOI] [PubMed] [Google Scholar]
  19. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  20. Malter J. S. Identification of an AUUUA-specific messenger RNA binding protein. Science. 1989 Nov 3;246(4930):664–666. doi: 10.1126/science.2814487. [DOI] [PubMed] [Google Scholar]
  21. Meeker T. C., Nagarajan L., ar-Rushdi A., Rovera G., Huebner K., Croce C. M. Characterization of the human PIM-1 gene: a putative proto-oncogene coding for a tissue specific member of the protein kinase family. Oncogene Res. 1987 Jun;1(1):87–101. [PubMed] [Google Scholar]
  22. Meijer D., Hermans A., von Lindern M., van Agthoven T., de Klein A., Mackenbach P., Grootegoed A., Talarico D., Della Valle G., Grosveld G. Molecular characterization of the testis specific c-abl mRNA in mouse. EMBO J. 1987 Dec 20;6(13):4041–4048. doi: 10.1002/j.1460-2075.1987.tb02749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nagarajan L., Louie E., Tsujimoto Y., ar-Rushdi A., Huebner K., Croce C. M. Localization of the human pim oncogene (PIM) to a region of chromosome 6 involved in translocations in acute leukemias. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2556–2560. doi: 10.1073/pnas.83.8.2556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oyen O., Myklebust F., Scott J. D., Cadd G. G., McKnight G. S., Hansson V., Jahnsen T. Subunits of cyclic adenosine 3',5'-monophosphate-dependent protein kinase show differential and distinct expression patterns during germ cell differentiation: alternative polyadenylation in germ cells gives rise to unique smaller-sized mRNA species. Biol Reprod. 1990 Jul;43(1):46–54. doi: 10.1095/biolreprod43.1.46. [DOI] [PubMed] [Google Scholar]
  25. Padma R., Nagarajan L. The human PIM-1 gene product is a protein serine kinase. Cancer Res. 1991 May 1;51(9):2486–2489. [PubMed] [Google Scholar]
  26. Reeves R., Elton T. S., Nissen M. S., Lehn D., Johnson K. R. Posttranscriptional gene regulation and specific binding of the nonhistone protein HMG-I by the 3' untranslated region of bovine interleukin 2 cDNA. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6531–6535. doi: 10.1073/pnas.84.18.6531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reeves R., Magnuson N. S. Mechanisms regulating transient expression of mammalian cytokine genes and cellular oncogenes. Prog Nucleic Acid Res Mol Biol. 1990;38:241–282. doi: 10.1016/s0079-6603(08)60713-8. [DOI] [PubMed] [Google Scholar]
  28. Reeves R., Spies G. A., Kiefer M., Barr P. J., Power M. Primary structure of the putative human oncogene, pim-1. Gene. 1990 Jun 15;90(2):303–307. doi: 10.1016/0378-1119(90)90195-w. [DOI] [PubMed] [Google Scholar]
  29. Sandberg M., Skålhegg B., Jahnsen T. The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals. Biochem Biophys Res Commun. 1990 Feb 28;167(1):323–330. doi: 10.1016/0006-291x(90)91768-n. [DOI] [PubMed] [Google Scholar]
  30. Saris C. J., Domen J., Berns A. The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG. EMBO J. 1991 Mar;10(3):655–664. doi: 10.1002/j.1460-2075.1991.tb07994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Selten G., Cuypers H. T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A. The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases. Cell. 1986 Aug 15;46(4):603–611. doi: 10.1016/0092-8674(86)90886-x. [DOI] [PubMed] [Google Scholar]
  33. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  34. Slaughter G. R., Means A. R. Analysis of expression of multiple genes encoding calmodulin during spermatogenesis. Mol Endocrinol. 1989 Oct;3(10):1569–1578. doi: 10.1210/mend-3-10-1569. [DOI] [PubMed] [Google Scholar]
  35. Sorrentino V., McKinney M. D., Giorgi M., Geremia R., Fleissner E. Expression of cellular protooncogenes in the mouse male germ line: a distinctive 2.4-kilobase pim-1 transcript is expressed in haploid postmeiotic cells. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2191–2195. doi: 10.1073/pnas.85.7.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Uhler M. D., Carmichael D. F., Lee D. C., Chrivia J. C., Krebs E. G., McKnight G. S. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1300–1304. doi: 10.1073/pnas.83.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Van Beveren C., Verma I. M. Homology among oncogenes. Curr Top Microbiol Immunol. 1986;123:73–98. doi: 10.1007/978-3-642-70810-7_4. [DOI] [PubMed] [Google Scholar]
  38. Wickens M. How the messenger got its tail: addition of poly(A) in the nucleus. Trends Biochem Sci. 1990 Jul;15(7):277–281. doi: 10.1016/0968-0004(90)90054-f. [DOI] [PubMed] [Google Scholar]
  39. Wingett D., Reeves R., Magnuson N. S. Stability changes in pim-1 proto-oncogene mRNA after mitogen stimulation of normal lymphocytes. J Immunol. 1991 Nov 15;147(10):3653–3659. [PubMed] [Google Scholar]

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